title: Genetic polymorphisms of matrix metalloproteinases and clinical outcomes in colorectal cancer patients.
abstract: BACKGROUND
  Colorectal cancer metastasis is a multistep process involving degradation of extracellular matrix components by proteolytic enzymes. Among them, matrix metalloproteinases (MMPs) are the principal degrading enzymes and their expressions/activities are also correlated with survival. Much research has showed the associations between genetic polymorphisms in MMPs and risk of colorectal cancer; however, their prognostic significance has not been well determined.
  
  
  METHODS
  We selected and genotyped 4 cancer-associated single nucleotide polymorphisms (SNPs) in a cohort of 282 colorectal cancer patients. The associations of these SNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis, Cox regression model, and survival tree analysis.
  
  
  RESULTS
  The relative risks of developing distant metastasis after curative surgery were higher in individuals with minor homozygote AA genotype than in those with GG/GA genotypes at MMP2 rs243866 (P = 0.012). Survival tree analysis also identified a higher-order genetic interaction profile consisting of MMP2 rs243866 and MMP2 rs2285053 that was significantly associated with distant metastasis-free survival (P trend = 0.016). After adjusting for possible confounders, the genetic interaction profile remained significant (P trend = 0.050).
  
  
  CONCLUSIONS
  These results suggest that genetic variations in the MMP2 might be potential predictors of distant metastasis-free survival after curative surgery.
authors.affiliation: Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ting
authors.forename: Lu-Min
authors.initials: LM
authors.lastname: Chen
authors.forename: Jiunn-Bey
authors.initials: JB
authors.lastname: Pao
authors.forename: Ying-Pi
authors.initials: YP
authors.lastname: Yang
authors.forename: Bang-Jau
authors.initials: BJ
authors.lastname: You
authors.forename: Ta-Yuan
authors.initials: TY
authors.lastname: Chang
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lan
authors.forename: Hong-Zin
authors.initials: HZ
authors.lastname: Lee
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Bao
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D020782:Matrix Metalloproteinases
keywords: colorectal cancer; matrix metalloproteinases; metastasis; single nucleotide polymorphism; survival.